An efficient molecular docking using conformational space annealing.

Molecular docking falls into the general category of global optimization problems because its main purpose is to find the most stable complex consisting of a receptor and its ligand. Conformational space annealing (CSA), a powerful global optimization method, is incorporated with the Tinker molecular modeling package to perform molecular docking simulations of six receptor-ligand complexes (3PTB, 1ULB, 2CPP, 1STP, 3CPA, and 1PPH) from the Protein Data Bank. In parallel, Monte Carlo with the minimization (MCM) method is also incorporated into the Tinker package for comparison. The energy function, consisting of electrostatic interactions, van der Waals interactions, and torsional energy terms, is calculated using the AMBER94 all-atom empirical force field. Rigid docking simulations for all six complexes and flexible docking simulations for three complexes (1STP, 3CPA, and 1PPH) are carried out using the CSA and the MCM methods. The simulation results show that the docking procedures using the CSA method generally find the most stable complexes as well as the native-like complexes more efficiently and accurately than those using the MCM, demonstrating that CSA is a promising search method for molecular docking problems.